The following proposal combines the strengths of in vivo and in vitro investigations in the same patients to evaluate altered insulin sensitivity in myotonic dystrophy and to contrast our findings with patients having other neuromuscular disorders and normal volunteers. Whole body studies of oral glucose and intravenous insulin tolerance will be made in all subjects. Intrabrachial arterial insulin infusions will be given to each participant. Larger doses of insulin will be administered to those myotonic dystrophy patients showing muscle insulin resistance to the initial insulin dose (the level reached with the initial infusion approximates the peak values in normals during oral glucose tolerance testing). In vitro studies of fibroblasts, monocytes, and fat cells from myotonic dystrophy and other neuromuscular diseased patients as well as normal subjects will be performed to examine insulin receptor numbers and, where appropriate, evaluate specific insulin actions. Our preliminary investigations have demonstrated a unique condition in myotonic dystrophy. There is marked forearm muscle hyporesponsiveness to insulin stimulated glucose uptake in the presence of normal basal insulin levels, normal intravenous insulin tolerance, and normal glucose tolerance with hyperinsulinism. There appears to be tissue specific insulin resistance in myotonic dystrophy and these investigations will extend our understanding of this altered responsiveness. At the same time the study results will provide informaion about the regulation of insulin receptor numbers in the presence of periodic hyperinsulinism and normal basal insulin concentration. Moreover, if specific muscle insulin resistance in myotonic dystrophy includes diminished uptake of amino acids as well as glucose, the information we will obtain may advance our understanding of the pathophysiology of muscle wasting in this disorder.